F9 p.Arg46Trp
c.136A>T · VCV3340055
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5519 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5519 | ambiguous |
|---|---|---|
| REVEL | 0.85 | moderately pathogenic-leaning |
| SaProt | LLR -12.56 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 5.2, phastCons 1 |
| Regional constraint | o/e 0.57 | unconstrained · MANE · 25 kb · p 2.3e-14 · regional, not allelic |
| Overall | ||
| CADD | 27.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- F9
- Protein
- p.Arg46Trp
- Coding
- c.136A>T
- MANE Select
- NM_000133
- Type
- single nucleotide variant
- Location
- chrX:139537057 (GRCh38)
- Structure
- AlphaFold pLDDT 80.45 · 57 PDB
- Residue 46
- a UniProt-annotated variant site (in hemb; severe); a UniProt-annotated variant site (in hemb; severe; cambridge; impaired processing of the propeptide; impaired gamma-carboxylation; decreased protein abundance; loss of function in blood coagulation)
Similar variants
- F9 p.Arg46Thr Uncertain significance ★ ⚠ same residue
- F9 p.Arg46Ser Pathogenic same residue
- F9 c.520+13A>G Pathogenic ★★★ same type
- F9 c.88+1G>A Pathogenic ★★★ same type
- F9 c.88+5G>T Likely pathogenic ★★★ same type
- F9 p.Ala279Thr Pathogenic ★★★ ⚠ same type
- F9 p.Ala337Pro Likely pathogenic ★★★ same type
- F9 p.Ala337Thr Pathogenic ★★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/f9-p-arg46trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown